Citalopram is a well known antidepressant drug that has now been on the market for some years and has the following structure: 
It is a selective, centrally active serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor, accordingly having antidepressant activities. The antidepressant activity of the compound has been reported in several publications, e.g. J. Hyttel, Prog. Neuro-Psychopharmacol. & Biol. Psychiat., 1982, 6, 277-295 and A. Gravem, Acta Psychiatr. Scand., 1987, 75, 478-486.
Citalopram is prepared by the process described in U.S. Pat. No. 4,650,884, according to which 5-cyanophthalide is subjected to two successive Grignard reactions, i.e. with 4-fluorophenyl magnesium halogenide and N,N-dimethylaminopropyl magnesium halogenide, respectively, and the resulting compound of the formula is subjected to a ring closure reaction by dehydration with strong sulfuric acid.
Enantiomers of citalopram may be prepared by the method described in U.S. Pat. No. 4,943,590, i.e. by separating the enantiomers of the intermediate of Formula II and performing enantioselective ring closure in order to obtain the desired enantiomer.
Thus, 5-cyanophthalide is an important intermediate for the manufacture of citalopram and it is important to produce this material in an adequate quality, by a convenient process and in a cost-effective way.
A method for the preparation of 5-cyanophthalide has previously been described in Bull. Soc. Sci. Bretagne, 1951, 26, 35 and in Levy and Stephen, J. Chem. Soc., 1931, 867. By this method 5-aminophthalide is converted to the corresponding 5-cyanophthalide by diazotation followed by reaction with CuCN. 5-Aminophthalide was obtained from 4-aminophthalimide by a two step reduction procedure.
Synthesis of certain alkyl- and phenylnitriles from acid chlorides is described in Tetrahedron Letters, 1982, 23, 14, 1505-1508, and in Tetrahedron, 1998, 54, 9281.
It has been found that 5-cyanophthalide may be prepared in high yields by a convenient, cost-effective procedure from the 2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)oxazoline or -thiazoline intermediates of Formula IV.